Detection of TP53 mutation, loss of heterozygosity and DNA content in fine-needle aspirates of breast carcinoma.
Recent preclinical and clinical data suggest that TP53 status and TP53 mutations may be important in determining tumour aggressiveness and therapy response. In this study we investigate the feasibility of a structural and quantitative analysis of TP53 on fine-needle aspiration (FNA) material obtained from 31 consecutive female patients with breast carcinoma, enrolled in a primary chemotherapy protocol. Tumours were screened for p53 protein overexpression and TP53 mutations (exons 5-8) using immunocytochemistry, polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and DNA sequencing analyses, and finally using fluorescence in situ hybridization (FISH) analysis. Positive nuclear staining was identified in six cases whereas mutations were detected in nine. Although the immunoreactive pattern fitted fully with the characterized TP53 mutation type, the considerable number of null p53 mutations (i.e. four) coupled with the lack of information regarding the localization of TP53 mutations make immunocytochemistry an inadequate indicator of TP53 function deregulation. Combining molecular and FISH analyses, we detected three cases with TP53 deletion and one case with deletion and mutation. Finally, DNA static-image analysis performed on 29 cases showed aneuploidy in 26 cases, which included all TP53-mutated cases. The present results show that FNA may assist clinical decisions by allowing the evaluation of a variety of biological parameters relevant for prognosis and treatment planning.
Lavarino
C
C
Division of Anatomical Pathology and Cytology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.
Corletto
V
V
Mezzelani
A
A
Della Torre
G
G
Bartoli
C
C
Riva
C
C
Pierotti
M A
MA
Rilke
F
F
Pilotti
S
S
D000328:Adult; D000368:Aged; D001707:Biopsy, Needle; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism; D004273:DNA, Neoplasm / Q000032:analysis*; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D019656:Loss of Heterozygosity / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000235:genetics*
D004273:DNA, Neoplasm; D016159:Tumor Suppressor Protein p53